KR20190034693A - Growth hormone secretion promoter - Google Patents

Abstract

It is an object of the present invention to provide a growth hormone secretagogue which is excellent in growth hormone secretion promoting effect and which can be administered orally. The growth hormone secretagogue of the present invention contains, as an active ingredient, at least one member selected from the group consisting of S-adenosyl methionine and / or its salt, Siberian larch leaf extract, olive extract, and stilbene compound. S-adenosylmethionine and / or a salt thereof may be contained in the form of S-adenosylmethionine and its salt itself produced by chemical synthesis, or may be a cell body containing S-adenosylmethionine and / or a salt thereof or It may be a culture. The stilbene-based compound may be a plant extract of vitaceac or Gnetaceae. The olive extract may be an extract which is separated from the fruit of the olive.

Description

Growth Hormone Secretion Promoter {GROWTH HORMONE SECRETION PROMOTER}

The present invention relates to a growth hormone secretagogue. More particularly, the present invention relates to a growth hormone secretagogue containing S-adenosylmethionine as an active ingredient.

Growth hormone (hereinafter sometimes abbreviated as GH) is secreted from the pituitary gland and is involved in metabolism such as bone metabolism, protein metabolism, sugar metabolism, fat metabolism, and electrolytic metabolism. The failure of growth hormone secretion leads to developmental disability in childhood, and is a risk factor for diseases such as metabolic disorders and cardiovascular disorders in adulthood. Even in normal people, the secretion of growth hormone decreases with age. In the elderly, it is known that they are in a state of growth hormone secretion relative to that of young people, and there are some points that the growth hormone secretion deficiency is leading to a deterioration of the quality of life of the elderly.

It is known that administration of the growth hormone per se to the growth hormone secretion deficiency of the child can provide effects such as improvement of growth growth disorder. It has been found that administration of growth hormone itself to adulthood-deficient growth hormone in adulthood can reduce the risk factors of diseases such as metabolic disorders. It is known that the administration of the growth hormone itself to the growth hormone secretion deficiency of the elderly can improve the quality of life and the like. However, in the method of administering the growth hormone itself, it is necessary to strictly administer the administration conditions such as the dose control, and it is necessary to control the medical expert. In addition, since growth hormone is a peptide, administration of growth hormone is required not only for oral administration but also for injection, and injection administration is also invasive (invasive).

A substance having an action of promoting the secretion of growth hormone in vivo is called a growth hormone secretion promoting substance. There has been proposed a method for promoting the secretion of growth hormone in vivo by using a growth hormone secretagogue which can be orally administered instead of administering the growth hormone per se. This method is thought to be a safer growth hormone secretion countermeasure because the action is milder than the administration of the growth hormone itself.

As a growth hormone secretagogue that can be administered orally, probiotics such as prebiotics such as dietary fiber and lactic acid bacteria (Patent Document 1: Japanese Patent Application Publication No. 2007-131541) and soybean protein derived peptides (Patent Document 2: Japanese Patent Application Laid- -347946), and γ-aminobutyric acid obtained by lactic acid fermentation (Patent Document 3: Japanese Patent Application Laid-Open No. 2004-269361).

However, the effect of the conventional growth hormone secretagogue promoting material was not satisfied.

Patent Document 1: Japanese Patent Application Laid-Open No. 2007-131541 Patent Document 2: JP-A-2006-347946 Patent Document 3: Japanese Patent Application Laid-Open No. 2004-269361

It is an object of the present invention to provide a growth hormone secretagogue which is excellent in growth hormone secretion promoting effect and which can be administered orally.

The inventors of the present invention have conducted intensive studies to solve the above problems and found that S-adenosylmethionine effectively promotes growth hormone secretion.

The present invention provides a growth hormone secretagogue using the following constitution based on the above findings.

[1] A growth hormone secretion promoter comprising, as an active ingredient, at least one member selected from the group consisting of S-adenosyl methionine and / or its salt, Siberian larch leaf extract, olive extract, and stilbene compound.

[2] The growth hormone secretion promoter according to [1], wherein the S-adenosyl methionine and / or its salt is a chemically synthesized S-adenosyl methionine and / or its salt.

[3] The growth hormone secretion promoter according to [1], wherein the S-adenosyl methionine and / or its salt is a cell containing S-adenosyl methionine and / or a salt thereof or a culture thereof.

[4] The growth hormone secretagogue according to [3], wherein the cells are yeast.

[5] The growth hormone secretion promoter according to any one of [1] to [4], wherein the stilbene compound is a plant extract derived from a stilbene compound.

[6] The plant growth regulator according to the above [5], wherein the plant extract derived from a stilbene compound is a plant extract of Gnetaceae containing a plant-derived extract or a stilbene-based compound containing a stilbene-based compound .

[7] The growth hormone secretagogue according to any one of [1] to [6], wherein the olive extract is an extract which is separated from the olive fruit.

[8] The pharmaceutical composition according to any one of [1] to [7], wherein the olive extract is an olive extract comprising at least one polyphenol selected from the group consisting of hydroxysterols, thyrosols and oleuropeins Described growth hormone secretagogue.

[9] A food or drink, a medicament or a quasi-drug comprising at least one selected from the group consisting of S-adenosyl methionine and / or its salt, Siberian larch extract, olive extract, and stilbene compound.

The present invention also provides a method for promoting secretion of growth hormone described below.

[10] A method for promoting the secretion of growth hormone in a living body by administering at least one member selected from the group consisting of S-adenosyl methionine and / or a salt thereof, Siberian larch leaf extract, olive extract, and stilbene- Way.

[11] The method according to [10], wherein the S-adenosyl methionine and / or its salt is chemically synthesized S-adenosyl methionine and / or a salt thereof, which promotes the secretion of the growth hormone in vivo.

[12] S-adenosyl methionine and / or a salt thereof is a method for promoting the secretion of a growth hormone in vivo according to [10], which is a microorganism containing S-adenosyl methionine and / or a salt thereof or a culture thereof .

[13] A method for promoting secretion of growth hormone in vivo according to [12] above, wherein the cells are yeasts.

[14] A method for promoting secretion of a growth hormone in vivo according to [10], wherein the stilbene compound is a plant extract derived from a stilbene compound.

[15] The method according to [10], wherein the plant extract containing a stilbene compound is a plant extract of grapevine comprising a stilbene-based compound or a plant extract of a plant containing the stilbene-based compound, How to promote.

[16] The method for promoting the secretion of in vivo growth hormone according to [10], wherein the olive extract is an extract isolated from olive fruit.

[17] the secretion of the in vivo growth hormone according to [10], wherein the olive extract is an olive extract comprising at least one polyphenol selected from the group consisting of hydroxcitrosols, thyrosols, and oleoprofen How to promote.

[18] A food, medicament or quasi-drug comprising at least one member selected from the group consisting of S-adenosyl methionine and / or its salt, Siberian larch leaf extract, olive extract, and stilbene- , A method for promoting the secretion of growth hormone in vivo.

According to the present invention, it is possible to provide a growth hormone secretagogue which can be administered orally and is excellent in growth hormone secretion promoting effect.

In the present invention, the active ingredient of the growth hormone secretagogue is at least one selected from the group consisting of S-adenosylmethionine and / or its salt, stilbene compound, olive extract, and Siberian larch leaf extract. In the present invention, as the active ingredient of the growth hormone secretagogue, one selected from the above group may be used alone, or a combination of two or more thereof may be used.

(1) S-adenosylmethionine and / or a salt thereof

Adenosylmethionine plays an important role in methylation such as promoting phospholipid metabolism, methylation of protein, methylation of nucleic acid and the like, in which the S-adenosylmethionine acts as a methyl group donor in a methylation reaction in vivo. have. However, it has not been known that administration of S-adenosyl methionine and / or its salt to a living body promotes the secretion of growth hormone in a living body.

S-adenosylmethionine has a structure in which adenosine and methionine are methylsulfonyl-bonded. Examples of the optical isomer of methionine include an L-isomer, a D-isomer, and a DL-isomer. In the present invention, methionine in the structure of S-adenosylmethionine may be any of the above optical isomers, but it is preferably L in view of physiological activity.

Examples of the salt of S-adenosylmethionine include sulfate, p-toluenesulfonate, sulfate p-toluenesulfonate, methanesulfonate, trifluoromethanesulfonate, 1,4-butane disulfonate, Pentanesulfonic acid, phosphates, chlorides, bromides, and the like. Any of these salts can be used as an active ingredient of the growth hormone secretagogue of the present invention.

In the present invention, S-adenosylmethionine and / or a salt thereof may be S-adenosylmethionine and / or a salt thereof obtained by chemical synthesis, and may be a bacterial cell containing S-adenosylmethionine and / or a salt thereof .

The microbial cells containing S-adenosylmethionine and / or its salt may be a microorganism originally containing S-adenosylmethionine and / or a salt thereof, and may be a microorganism which contains no S-adenosylmethionine and / Adenosylmethionine and / or a salt thereof may be produced by using a method of producing silymethionine and / or a salt thereof in a cell. Examples of a method of producing S-adenosylmethionine and / or its salt in cells include culturing the cells to produce S-adenosylmethionine and / or its salt in the cells (intracellular). In the case of such a method, it is possible to obtain a culture obtained, a culture solution, cells recovered after culturing, dried cells obtained by drying the cells, cell purified water obtained by purifying a culture or a culture solution, and dried cell- Either one may be used.

The type of the cell is not particularly limited, but yeast is preferable. The kind of yeast may be any as long as it produces S-adenosylmethionine and is orally administrable. For example, yeasts belonging to the genus Saccharomyces can be mentioned, and Saccharomyces cerevisia is suitable.

In the present invention, S-adenosylmethionine and / or a salt thereof may be used singly or in combination of two or more species derived from a specific origin or production method.

When the growth hormone secretagogue according to the present invention is used as a medicine, the S-adenosylmethionine and / or its salt can be produced by a chemically synthesized S-adenosylmethionine and / or its salt, S-adenosylmethionine and / A cell containing the salt or a culture thereof is preferable. When the growth hormone secretagogue according to the present invention is used as a food, the S-adenosyl methionine and / or its salt is preferably the above-mentioned microorganism or a culture thereof, more preferably a yeast or a culture thereof.

When the growth hormone secretagogue of the present invention contains S-adenosyl methionine and / or its salt as an active ingredient, the dose of the growth hormone secretagogue is not particularly limited as long as the effect of the present invention is not impaired, The age and condition of the subject to be administered, and the like. In the case where there is no problem such as excessive growth hormone secretion in the subject's administered organism, the dosage per day for obtaining the desired effect is usually 1 to 2000 mg as a daily dose of S-adenosyl methionine and / or its salt , Preferably 10 to 1600 mg, more preferably 10 to 600 mg, and still more preferably 20 to 100 mg.

As the yeast containing S-adenosylmethionine and / or its salt, dry yeast is preferable. In the present invention, a commercially available product of yeast containing S-adenosylmethionine and / or its salt may be used. Examples of commercially available products include "SAMe high-content dry yeast (trade name)" manufactured by Mitsubishi Gas Chemical Co., Ltd., "Spearse (trade name)" manufactured by Itariagunosys, "Ami (trade name)" manufactured by Iwata Chemical Industry Co., .

(2) Stilbene compound

The stilbene compound is a compound having a stilbene skeleton. The stilbene skeleton is shown in formula (I).

[Chemical Formula 1]

The stilbene skeleton may be substituted with a functional group. The substitution site by the functional group is not particularly limited, but usually it is an aromatic ring. Examples of such a functional group include a hydroxyl group (hydroxyl group), an alkyl group, a hydroxyalkyl group, an amino group, a sulfone group, and a phosphoric acid group. Among them, a hydroxyl group and a hydroxyalkyl group are preferable.

The stilbene compound may be a monomer, a multimer, a glycoside of a monomer, or a glycoside of a multimer if it has a stilbene skeleton. Among them, a monomer having a hydroxyl group and a hydroxyalkyl group as a functional group, a polymer and a glycoside thereof are preferable. Examples of the monomer include Resveratrol, Piceatannol, Astringin, Pterostilbene, and the like. The glycosides of the monomers include, for example, Piceid. Examples of the oligomers include, but are not limited to, δ-viniferin, ε-viniferin, Gnetin C, Gnetin L, α- viniferin, Ampelopsin A, and the like. Examples of the glycosides of the multimer include Gnemonoside A, Gnemonoside C, and Gnemonoside D.

The above compounds are classified as resveratrol (s). Resveratrol has been shown to be effective in reducing ischemic cardiovascular effects (Lancet, 338, 1523-1526, 1992), anticancer effects (Br. J. cancer, 86, 774-778, 2002) 167, 648-691, 2008), hypertension inhibitory effect (Eur. J. Pharmacol., 667, 258-264, 2011) and life extension effect (Nature, 444, 337-342, 2006) . The stilbene compound is preferably at least one compound selected from resveratol.

In the present invention, the stilbene-based compound may be a stilbene-based compound obtained by chemical synthesis, or a stilbene-based compound derived from a natural origin (for example, a bacterium or a plant). Of these, naturally occurring stilbene compounds are preferred, and plant-derived stilbene compounds are preferred.

The naturally occurring stilbene compound is not necessarily a pure stilbene compound and may be a mixture with another compound. Examples of the mixture include plant extract extracts, part or all of plants, and cell culture. Of these, plant extracts are preferred.

When a plant extract is used as a stilbene compound, a plant extract of a plant containing a stilbene compound may be used. Examples of the plant containing the stilbene compound include grape plants, bamboo plants, bamboo plants, bamboo plants, and neta plants. Among them, grape plants or netta plants are preferred.

The grape plant may contain a stilbene compound, and preferably contains resveratrol. The grape plants include, for example, Vitis vinifera, Vitis labrusca, Vitis california, Vitis amurensis, · Species such as Vitis coignetiae, Vitis shiragai, and the like. Examples of grape plants include Cabernet Sauvignon, Merlot, Pinot Noir, Gema, Shirah, Naviolo, Sangiovese, Temprani, Zampadel, Carmenere, Malbec, Muscat Bailey A, Koshu, Sauvignon Blanc , Chamondo, Chardonnay, Muscatade, Riesling, Musca, Viognier, Trevisiano, Pinot Grigor, Purmint, Palomino and others.

The neta plant is not particularly limited as long as it is a species containing resveratrol. Examples of the neta plant include Gnetum gnemon, Gnetum brunonianum, Gnetum latifolium, Gnetum tenuifolium, and the like. have. Among them, Natumbinemon is preferable.

The extracting part of the plant is not particularly limited and may be all or part of the plant (for example, leaves (leaves, stems, vines, leaves, fruits, seeds) Seeds or fruits are preferred, and those of lettuce, seeds or fruit are more preferable, and those of fruit exudate (fruit, seed or fruit) are preferable, Is more preferable.

When a part of the plant is used, the part separated from the plant may be used as it is, or may be dried by the sun, a machine, or the like.

The extraction method is not particularly limited, and examples thereof include a method of extracting using a solvent, and a method of extracting using a supercritical extraction method using carbon dioxide or the like. In the extraction method using a solvent, examples of the extraction solvent include water, methanol, ethanol n-propanol, isopropanol, acetone, methyl ethyl ketone, methyl butyl ketone, ethyl acetate, ethylene glycol, propylene glycol, glycerin, , Propionic acid, and the like. These extraction solvents may be used either singly or in the form of a mixture of two or more. The extraction solvent is preferably water, ethanol or a mixture thereof (hydrous ethanol). When the functional ethanol is used, the alcohol concentration is not limited, but is preferably 20 to 90% by volume, more preferably 40 to 80% by volume.

In addition, a plant extract may be used, or a stilbene compound obtained by purifying the plant extract may be used.

The grape-extracted extract and melin-coarse extract are commercially available, and commercially available products can be used in the present invention. Examples of commercially available grape extract include "VINEATROL 20M (trade name)" (manufactured by ACTICHEM) and the like. Examples of commercially available products of melin extract include "Melin Jo Reservatrol 20 (trade name)" (manufactured by Luna YBF Co., Ltd.) and the like.

When the growth hormone secretagogue of the present invention contains a stilbene-based compound as an active ingredient, the dose of the growth hormone secretagogue is not particularly limited as long as the effect of the present invention is not impaired, and the age, And can be appropriately changed depending on factors such as the state. In the case where there is no problem such as excessive growth hormone secretion in the subject's body to be administered, the daily dose to obtain the desired effect is usually 0.1 to 1000 mg, preferably 1 to 500 mg, per day as an intake amount of the stilbene- , More preferably from 10 to 200 mg, and still more preferably from 20 to 120 mg.

(3) olive extract

Olive extract has been conventionally known to have antioxidant activity, prevention of heart disease and cancer (Free Radical Biology & Medicine, 40, 608-616, 2006), and anti-inflammatory action (J. Nutr., 1475-1479, 2005) have. However, it has not been known that olive extract has an action of promoting the secretion of growth hormone in a living body by administering it to a living body.

Olive extract is an extract that is isolated from all or part of the plant of olive (Olea europea L.). The whole or part of the olive plant may be separated using an extraction solvent or may be separated by compression.

The separation site of the olive extract is not particularly limited, and may be all of the plant, and may be a part (e.g., a leaf, flower, fruit), but fruit is preferable.

As the extraction solvent, for example, water, an organic solvent (for example, one kind of solvent selected from alcohol, acetone, or a mixed solvent of two or more kinds), water and a mixed solution of an organic solvent can be used. Among them, water, a mixture of water and alcohol, and an alcohol are preferable. As the alcohol, ethanol methanol is preferable. The extraction time and temperature can be appropriately determined depending on the extraction site of olive extract, the kind of solvent, and the like. The olive extract may be a crude extract (crude extract) extracted from olive, or the crude extract may be subjected to processing such as concentration, drying, and pulverization. It is also possible to use a treatment by a distribution method or a purification treatment (for example, an adsorption treatment using an ion exchange resin, a column or the like, elution by a solvent, and then a concentration treatment if necessary) have.

When the olive extract is separated by squeezing, the object to be separated is preferably a fruit, more preferably a fruit in which olives are matured. For example, olive extract can be obtained by filtering and / or concentrating the juice obtained by pressing fruit. These filtrates and concentrates may be pulverized by spray drying or the like as required.

The form of the olive extract is not particularly limited, and powder or paste may be used.

Olives are generally rich in glycerides of fatty acids, such as glycerides of oleic acid, glycerides of linoleic acid, glycerides of palmitic acid, and fat-soluble vitamins, and include minerals such as potassium, phosphorus and magnesium. Olive oil contains lipophilic components such as unsaturated fatty acids,? -Carotene, vitamin D, E, and qualene dihydroquercetin, and polyphenols such as hydroxycortisol, tyrosol, and oleoprofen. In the present invention, the pulp and the oil component originally of olive are preferably excluded from the olive extract by operations such as compression, concentration (centrifugation, etc.).

In the present invention, the olive extract preferably contains polyphenols, and more preferably includes at least one polyphenol selected from the group consisting of hydroxystyrene, thyrosol, and oleoflavone. The content of the polyphenol in the olive extract is preferably high, and it is more preferable that the content of the at least one polyphenol selected from the group consisting of hydroxystyrene, thyrosol and oleoprofen is high.

Olive extracts are commercially available, and commercially available products can be used. Examples of commercial products of olive extract include "Olivex (trade name)" (GROUPE GRAP'SUD, France).

When the growth hormone secretagogue of the present invention contains olive extract as an active ingredient, the dosage of the growth hormone secretagogue is not particularly limited as long as the effect of the present invention is not impaired, and the age, condition And the like. In the case where there is no problem such as excessive growth hormone secretion in the subject's administered organism, the daily dose to obtain the desired effect is 0.1 to 1000 mg per day as the daily dose of olive extract, and 1 to 500 mg More preferably 10 to 200 mg, and still more preferably 20 to 180 mg.

(4) Siberian larch Extract

It is known that Siberian larch leaf extract has an antioxidative activity and an inhibitory action on melanin production. However, it has not been known that the administration of Siberian larch leaf extract to a living body promotes secretion of growth hormone in vivo.

The Siberian larch Extract is an extract of Siberian larch (Larix Sibirica), a Pinaceae orchid, distributed in Siberia and Far East. The Siberian larch Extract contains dihydroquercetin as its main ingredient and contains some other ingredients such as dihydrocanneverol and naringenin.

The Siberian larch Extract can be extracted from all or part of the Siberian larch plant using an extraction solvent. The extraction site of the Siberian larch is not particularly limited and may be all or a part of the plant (for example, a leaf, a bark, a tree, a seed or a flower), but a bark or a neck is preferable, Is more preferable. As the extraction solvent, for example, water, an organic solvent (for example, one kind of solvent selected from alcohol, acetone, or a mixed solvent of two or more kinds), water and a mixed solution of an organic solvent can be used. Among them, water, a mixture of water and alcohol, and an alcohol are preferable. As the alcohol, ethanol methanol is preferable. The extraction time and temperature can be appropriately determined by the extraction site of Siberian larch, the kind of solvent, and the like. The Siberian larch leaf extract may be a crude extract extracted from Siberian larch or may be obtained by subjecting the crude extract to concentration, drying, crushing, compression, and the like. It is also possible to use a treatment by a distribution method or a purification treatment (for example, an adsorption treatment using an ion exchange resin, a column or the like, elution by a solvent, and then a concentration treatment if necessary) have. On the other hand, 2091076 As described in the specification, the product obtained by finely grinding Siberian larch may be moistened with steam, extracted with acetone, and purified. The shape of the Siberian larch leaf extract is not particularly limited, and powder or paste may be used.

Siberian larch leaf extract is commercially available, and a commercial product can be used in the present invention. Examples of commercial products of Siberian larch Extract include "Dicubertin (trade name)" (Flavivar, Irkutsk City, Russia).

When the growth hormone secretagogue of the present invention contains Siberian larch larvae extract as an active ingredient, the dose of the growth hormone secretagogue is not particularly limited as long as the effect of the present invention is not impaired, and the age, And can be appropriately changed depending on factors such as the state. In the case where there is no problem such as excessive growth hormone secretion in the subject's administered organism, the daily dose to obtain the desired effect is usually 3 to 1000 mg, and 15 to 500 mg per day of Siberian larch leaf extract, More preferably from 20 to 200 mg, and still more preferably from 30 to 120 mg.

In the present invention, the Siberian larch larch extract may be used singly or in combination of two or more species having different extraction conditions under specific extraction conditions.

The growth hormone secretagogue promoter according to the present invention may be composed of at least one member selected from the group consisting of S-adenosyl methionine and / or its salts, Siberian larch extract, olive extract, and stilbene compound (that is, May account for 100% by mass of the whole), or may contain other components. Other components include, for example, a component for securing stability in storage and distribution, such as a storage stabilizer, and a part or all of components constituting the desired end product.

(Use of the growth hormone secretagogue of the present invention in the final product)

The growth hormone secretagogue of the present invention is characterized by comprising, as an active ingredient, one kind selected from the group consisting of S-adenosyl methionine and / or its salt, stilbene compound, olive extract, and Siberian larch leaf extract having a growth hormone secretagogue- Or more. S-adenosylmethionine and / or a salt thereof is originally a substance contained in a living body. The stilbene compounds are contained in plants such as grape plants, neta plants and the like, and the fruits of these plants generally eat and boil the stem and the vine. In Southeast Asia such as Indonesia, young leaves, flowers and fruit of neta plants are eaten as vegetables. Neta plant seeds are dried after they are dried to obtain dry seeds, and dried seeds are fried with oil and always eaten. Olives are generally eating fruit. The Siberian larch Extract has the nutrition of the indigenous peoples of eastern Russia and can therefore be administered safely and effectively to the growth hormone secretion in vivo. Therefore, all of these active ingredients can be safely administered to a living body, and can effectively promote growth hormone secretion.

The growth hormone secretagogue of the present invention may be used in the form of an end product as a final product (for example, a food, a medicine, a quasi drug, etc.). In addition, the growth hormone secretagogue of the present invention may be used as an additive for foods, medicines, and quasi-drugs. Thereby, it is possible to improve or alleviate the growth hormone secretion deficiency of the living body.

The growth hormone secretagogue of the present invention may have components (pharmacologically acceptable bases) other than the above-mentioned effective ingredients. As an example of the component other than the active ingredient, there may be mentioned a component (for example, a preservative stabilizer) which secures stability in storage and distribution. In addition, one or two or more kinds of components selected from various components constituting the desired end product (for example, a food, a medicine, a quasi drug, etc.) (preferably about one to three kinds, more preferably one kind Degree).

The components other than the active ingredient that can be included in the growth hormone secretagogue of the present invention are not particularly limited as long as the object of the present invention is not impaired. Examples of the additives include excipients, disintegrators, binders, lubricants, coating agents, coloring agents, coloring agents, flavoring agents, flavoring agents, antioxidants, preservatives, tastes, acidifiers, sweeteners, Vitamins, swelling agents, thickeners, surfactants, and the like. Among them, one or two or more kinds selected from those which do not impair various properties (for example, formulation stability) necessary for the preparation and which conform to the formulations of the final product (for example, medicines, quasi-drugs, have. In addition, other components having growth hormone secretion promoting effect may be combined.

When the growth hormone secretagogue enhancer contains two or more active ingredients, or when the growth hormone secretagogue enhancer has a component other than the active ingredient, it may be referred to as a composition for promoting the secretion of growth hormone secretion.

(Administration form of the growth hormone secretagogue of the present invention)

The dosage form of the growth hormone secretagogue of the present invention is not particularly limited. For example, oral administration (for example, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, percutaneous administration, (经 pulmonary) administration, etc.). Of these, a dosage form having low invasiveness is preferable, and oral administration is more preferable.

The formulation of the growth hormone secretagogue of the present invention can be appropriately determined depending on whether it is a food or drink, a medicine or a quasi-drug, and is not particularly limited. Examples of formulations for oral administration include liquid (liquid), syrup (syrup), tablets (tablet), capsules (capsules), powder (granules, fine particles), soft capsules Liquid form), syrup form (syrup form), solid form, semi-liquid form, cream form, paste form. Examples of the formulations for parenteral administration include intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, expulsion administration, and transpulmonary administration. Among them, a dosage form without invasion to a living body is preferable, and oral administration is preferable.

When the growth hormone secretagogue of the present invention is used as a food or drink, it is usually administered orally.

The growth hormone secretagogue of the present invention is useful as a food and drink, a medicament and a quasi-drug for alleviating growth hormone secretion deficiency because it can promote growth hormone secretion.

The subject to whom the growth hormone secretagogue of the present invention is to be ingested is not particularly limited. For example, a person who feels a crisis about a subject who is concerned about developmental growth disorder, a metabolic disorder, a cardiovascular disorder or the like, It is suitable for the person who wants to plan. In addition, even for a subject who has no particular problem, it can be routinely ingested for the purpose of promoting the secretion of growth hormone. The intake timing of the growth hormone secretagogue is not particularly limited.

The growth hormone secretagogue of the present invention can be used as various food and beverage products. For example, the present invention can be applied to beverages such as beverages (soft drinks, carbonated drinks, nutritional drinks, powdered beverages, fruit drinks, milk beverages, jelly beverages, etc.), confections (cookies, cakes, gums, candy, tablets, (Hamburger, ham, sausage, sausage, cheese, butter, yogurt, cream, cheese, margarine, fermented milk, etc.), processed fish products (fish paste, fish skewers, (Mayonnaise, shortening, dressing, sauce, seasoned broth, soy sauce, etc.), soup (powdered soup, liquid soup, etc.) have. The growth hormone secretagogue of the present invention can be used as a food or drink such as health food, functional food, nutritional supplement (supplement), specific health food, medical food, patient food, infant food, nursing food, have. Among them, health foods and functional foods are preferable, and health foods are more preferable.

In the present invention, the effect of promoting the secretion of growth hormone can be confirmed by the fact that the amount of growth hormone in the urine (urine) the next morning is increased compared to when the sample is taken to the paneler before going to bed, .

Example

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 and Comparative Example 1

As a sample of Example 1, a tablet (containing 80 mg of S-adenosylmethionine in 9 broths) containing S-adenosylmethionine-containing yeast was prepared. As a sample of Comparative Example 1, a tablet of a placebo (placebo) containing no S-adenosylmethionine-containing yeast was prepared. As the yeast containing S-adenosylmethionine, "Ami (trade name)" manufactured by Iwata Chemical Industry Co., Ltd. was used.

The respective compositions of the sample of Example 1 and the sample of Comparative Example 1 are as shown in Table 1 below.

[Table 1]

(Evaluation of growth hormone secretion promoting effect)

Thirteen adults as a panelist were given the sample of Example 1 above one hour before bed and the amount of growth hormone in the first urine (urine) (early morning urine) at the time of the next morning was measured. The sample of Comparative Example 1 was taken 1 hour before bedtime to 13 panelists as in Example 1, and the amount of growth hormone in the first urine at the time of the next morning was measured. The number of administration and measurement of each sample was three for each panelist. The mean sleep time of each panelist was 6.5 hours. The difference between the sleeping time of the paneler with the shortest sleeping time and the sleeping time with the longest sleeping time was 2 hours, and there was no significant difference.

The growth hormone secretion promoting effect was evaluated by the degree of increase in the amount of growth hormone (GH) in the urine.

(Correlation between an increase in the amount of GH in the urine and an increase in the amount of GH secreted in the body)

Since the amount of GH in the early morning urine correlates well with the amount of blood GH 3 hours after nighttime sleep, the measurement of the amount of GH in the early morning urine is used to measure the amount of GH by blood sampling (Clinical significance of urine growth hormone measurement, Yasuko Itagane et al., Pediatrics, Kanehara Publishing Co., 1989, vol. 80, No. 6, p. 629-636).

(Measurement of urinary GH amount)

The amount of GH in the urine was measured by a chemiluminescent enzyme immunoassay (CLEIA method) by an external clinical testing company (Esar Elsa). The CLEIA method is based on Adachi, Hormone and Clinical, Medical World History, published in 1997, Vol. 45, p. 223-235, which will be briefly described below. First, an anti (GH) mouse monoclonal antibody solid-phase-conjugated to GH of urine and a well of a microplate is reacted, and also a biotinylated anti-GH antibody is reacted with a peroxidase-labeled Label) Streptavidin is added. Subsequently, when hydrogen peroxide and luminol are added, light emission with intensity corresponding to the amount of GH is generated. Then, the emission intensity can be measured, and the amount of GH in the urine can be quantified from the calibration curve. In the evaluation in the present example, the creatinine concentration in urine was also measured and the amount of GH corrected for creatinine was determined.

(Mean value of urinary GH amount after S-adenosyl methionine ingestion) of the measured value (three times) of the GH amount (pg / mg · Cr) of urine of each of the panelists was calculated. In Comparative Example 1, the average value (the average value of urinary GH amount after taking the placebo) was calculated. The percent change in urinary GH amount (%) was calculated by the following equation (1) for each panel.

Equation (1):

(%) = (Average value of urinary GH amount after ingesting yeast containing S-adenosylmethionine) / (mean value of urinary GH amount after taking placebo) x 100

The mean value of the rate of change in urinary GH amount was 116.2%.

Example 2 and Comparative Example 2

Tests and evaluations were conducted in the same manner as in Example 1 except that samples having the compositions shown in Table 2 were used.

[Table 2]

The percent change in urinary GH amount (%) was calculated by the formula (1) for each panel. The mean value of the 13 persons in the change rate (%) of urinary GH amount was 112.4%.

The results of Examples 1 and 2 and Comparative Examples 1 and 2 show that the administration of S-adenosyl methionine and / or its salt to a living body effectively promotes the secretion of GH in the living body.

Hereinafter, a formulation of various compositions (final products) using the growth hormone secretagogue of the present invention is shown. As the S-adenosylmethionine-containing yeast, "SAMe high-content dry yeast (trade name)" manufactured by Mitsubishi Gas Chemical Co., Ltd. was used in the following formulation.

(Prescription Example 1: Tablets (1))

100 mg of S-adenosylmethionine-containing yeast, 60 mg of lactose, 80 mg of crystalline cellulose, 5 mg of carboxymethyl cellulose-Ca, and 5 mg of sucrose fatty acid ester were prepared and tableted by a conventional method.

(Prescription Example 2: Tablets (2))

Tablets were prepared by the routine method using the following ingredients:

108 mg of granules, 30 mg of S-adenosylmethionine-containing yeast, 110 mg of sorbitol, 15 mg of partially pregelatinized starch, 75 mg of magnesium phosphate, 3 mg of calcium stearate, 40 mg of menthol particles and 5 mg of aspartame .

The assembly was prepared by adding 1900 g of erythritol and 300 g of cornstarch to 4000 g of a 6% by mass aqueous solution of hydroxypropyl cellulose. The average particle diameter was 290 탆.

(Prescription Example 3: Soft Capsules (1))

The following ingredients were used to prepare the contents of the soft capsule:

200 mg of yeast containing S-adenosylmethionine; Vegetable oil 110 mg; Glycerin fatty acid ester 10 mg; Beeswax 10 mg.

Soft capsules were prepared by the usual method using the above ingredients and porcine gelatin.

Practical Example 3, Practical Example 4 and Comparative Example 3

As a sample of Example 3, a tablet containing a grape-extracted extract was prepared. As a sample of Example 4, a capsule preparation containing a melilin extract was prepared. As a sample of Comparative Example 3, purification of a placebo containing no grape-extracted extract and melancholia extract was prepared. As the grape extract, VINEATROL 20M (trade name) manufactured by ACTICHEM was used. As the melin crude extract, MELINY Jo Resveratrol 20 (trade name) manufactured by Luna YBF Co., Ltd. was used.

Examples of the examples of the growth hormone secretagogue according to the present invention and the compositions of the comparative samples are as shown in Table 3 below.

[Table 3]

(Evaluation of growth hormone secretion promoting effect)

Six adult volunteers as a panelist were allowed to consume the sample of Example 3 continuously one day before going to bed for four consecutive days and the amount of growth hormone in the first urine (early morning first urine) at the next morning was measured. Six men and 6 women on the same panel were instructed to consume the sample of Comparative Example 3 one hour before bed for the fourth consecutive week following the sample intake of Example 3, and the first urine at the time of the next morning Urine) were measured.

In addition, 6 men and 6 women in the same panel were allowed to take a sample of Example 4 consecutively for one hour before going to bed at the same time, and the amount of growth hormone in the first urine (early morning first urine) Respectively. In the same panel, 6 men were given the sample of Example 4, and the samples of Comparative Example 3 were consecutively consecutively consecutively for four consecutive weeks, and the first urine at the time of the next morning 1 < / RTI > urine) was measured.

The number of administration and measurement of each sample was 4 for each panelist. The mean sleep time of each panelist was 6.5 hours. The difference between the sleeping time of the paneler with the shortest sleeping time and the sleeping time with the longest sleeping time was 2 hours, and there was no significant difference.

The growth hormone secretion promoting effect was evaluated by the degree of increase in the amount of growth hormone (GH) in the urine.

(Measurement of urinary GH amount)

The amount of GH in urine was measured by a chemiluminescent enzyme immunoassay (CLEIA method) as in Example 1, and was performed by an external clinical testing company (Esar Elsa).

The average value (the average value of the urinary GH amount after ingestion of the sample of Example 3 and the sample of Example 4) of the measured value (four times) of the GH amount (pg / mg · Cr) of urine in each of the panelists was calculated. In Comparative Example 3, the average value (the average value of urinary GH amount after taking the placebo) was calculated. The change rate (%) of the GH amount in the urine was calculated by the following formula (2) for each panel.

Equation (2):

(%) = (Average value of urinary GH amount after ingestion of grape extract or melin extract) / (mean value of urinary GH amount after ingestion of placebo) x 100

The mean values of the six GH changes of grape - extracted and melilin extracts were 165.1% and 109.4%, respectively.

The results of Example 3, Example 4, and Comparative Example 3 show that by administering a stilbene-based compound to a living body, the secretion of GH in the living body is effectively promoted.

Hereinafter, a formulation of various compositions (final products) using the growth hormone secretagogue of the present invention is shown. In the following formulation, VINEATROL 20M (trade name) manufactured by ACTICHEM was used as the grape extract. MELINY Joe Resveratrol 20 (trade name) manufactured by Luna YBF Co., Ltd. was used as the melin extract.

(Prescription Example 4: Tablets (3))

140 mg of grape extract, 155 mg of crystalline cellulose, and 5 mg of sucrose fatty acid ester were tableted by a conventional method.

(Prescription Example 5: Soft Capsules (2))

The following ingredients were used to prepare the contents of the soft capsule:

140 mg of grape extract, 110 mg of vegetable oil, 10 mg of glycerin fatty acid ester, 10 mg of beeswax.

Soft capsules were prepared by the usual method using the above ingredients and porcine gelatin.

(Prescription Example 6: Tablets (4))

140 mg of melilin extract, 155 mg of crystalline cellulose and 5 mg of sucrose fatty acid ester were prepared by tableting by a conventional method.

(Prescription Example 7: Soft Capsules (3))

The following ingredients were used to prepare the contents of the soft capsule:

Melin extract, 140 mg of plant extract, 110 mg of vegetable oil, 10 mg of glycerin fatty acid ester, 10 mg of beeswax.

Soft capsules were prepared by the usual method using the above ingredients and porcine gelatin.

Example 5 and Comparative Example 4

As a sample of Example 5, a capsule preparation containing an olive extract was prepared. As a sample of Comparative Example 4, a capsule of a placebo containing no olive extract was prepared. As the olive extract, "Olivex (trade name)" made by GROUPE GRAP'SUD (France) was used.

Examples of the examples of the growth hormone secretagogue according to the present invention and the compositions of the comparative samples are shown in Table 4 below.

[Table 4]

(Evaluation of growth hormone secretion promoting effect)

Six adult volunteers as a panelist were allowed to take the sample of Example 5 1 hour before going to bed and the amount of growth hormone in the first urine (early morning first urine) at the time of the next morning was measured. Six of the panelists as in Example 5 were given a sample of Comparative Example 4 one hour before bedtime, and the next day, the amount of growth hormone in the first urine at the time of the weather was measured. The number of administration and measurement of each sample was 4 for each panelist. The mean sleep time of each panelist was 6.5 hours. The difference between the sleeping time of the paneler with the shortest sleeping time and the sleeping time with the longest sleeping time was 2 hours, and there was no significant difference.

The growth hormone secretion promoting effect was evaluated by the degree of increase in the amount of growth hormone (GH) in the urine.

(Measurement of urinary GH amount)

The amount of GH in urine was measured by a chemiluminescent enzyme immunoassay (CLEIA method) as in Example 1, and was performed by an external clinical testing company (Esar Elsa).

(Average value of urinary GH amount after ingestion of the sample of Example 5) of the measured value (four times) of the amount of GH (pg / mg · Cr) of urine in each of the panelists was calculated. In Comparative Example 4, the average value (the average value of urinary GH amount after taking the placebo) was calculated. The change rate (%) of urinary GH amount was calculated by the following formula (3) for each of the panelists.

Equation (3):

(%) = (Average value of urinary GH amount after ingesting olive extract) / (mean value of urinary GH amount after ingestion of placebo) x 100

The average value of the change rate of the urinary GH amount of olive extract was 254.7%.

The results of Example 5 and Comparative Example 4 show that by administering olive extract to a living body, the secretion of GH in the living body is effectively promoted.

Hereinafter, a formulation of various compositions (final products) using the growth hormone secretagogue of the present invention is shown. In the following formulation, "Olivex (trade name)" of GROUPE GRAP'SUD was used as an olive extract.

(Prescription Example 8: Tablets (5))

100 mg of olive extract, 190 mg of crystalline cellulose, 5 mg of carboxymethyl cellulose-Ca and 5 mg of sucrose fatty acid ester were prepared by tableting by a conventional method.

(Prescription Example 9: Tablets (6))

Tablets were prepared by the routine method using the following ingredients:

108 mg of the assembly, 100 mg of olive extract, 110 mg of sorbitol, 15 mg of partially pregelatinized starch, 75 mg of magnesium phosphate, 3 mg of calcium stearate, 40 mg of menthol particles and 5 mg of aspartame.

The assembly was prepared by adding 1900 g of erythritol and 300 g of cornstarch to 4000 g of a 6% by mass aqueous solution of hydroxypropyl cellulose. The average particle diameter was 290 탆.

(Prescription Example 10: Soft Capsules (4))

The following ingredients were used to prepare the contents of the soft capsule:

100 mg of olive extract, 110 mg of vegetable oil, 10 mg of glycerin fatty acid ester, 10 mg of beeswax.

Soft capsules were prepared by the usual method using the above ingredients and porcine gelatin.

Example 6 and Comparative Example 5

As a sample of Example 6, a tablet (containing 60 mg of Siberian larch leaf extract in 6 liters) containing a Siberian larch leaf extract was prepared. As a sample of Comparative Example 5, a tablet of Siberian larch leaf extract-free placebo was prepared. As Siberian larch leaf extract, " Dicbertin (trade name) " of Flavivir was used. The Siberian larch leaf extract contains 90% by mass, 8% by mass and 2% by mass of dihydroquercetin, dihydrocanneverol and naringenin, respectively.

Examples of the examples of the growth hormone secretagogue of the present invention and the compositions of the comparative samples are shown in Table 5 below.

[Table 5]

(Evaluation of growth hormone secretion promoting effect)

Thirteen adult male and female panelists were allowed to take the sample of Example 6 1 hour before going to bed and the amount of growth hormone in the first urine (early morning first urine) at the time of the next morning was measured. 13 of the panelists of Example 6 were given a sample of Comparative Example 5 one hour before bedtime and the next day, the amount of growth hormone in the first urine at the time of the weather was measured. The number of administration and measurement of each sample was three for each panelist. The mean sleep time of each panelist was 6.5 hours. The difference between the sleeping time of the paneler with the shortest sleeping time and the sleeping time with the longest sleeping time was 2 hours, and there was no significant difference.

The growth hormone secretion promoting effect was evaluated by the degree of increase in the amount of growth hormone (GH) in the urine.

(Measurement of urinary GH amount)

The amount of GH in urine was measured by a chemiluminescent enzyme immunoassay (CLEIA method) as in Example 1, and was performed by an external clinical testing company (Esar Elsa).

(Mean value of urinary GH amount after ingestion of each sample of Example 6) of the measured value (three times) of the amount of GH (pg / mg · Cr) of urine in each of the panelists was calculated. In Comparative Example 5, the average value (the average value of urinary GH amount after taking the placebo) was calculated. The percent change in the urinary GH amount (%) was calculated by the following formula (4) for each of the panelists.

Equation (4):

(%) = (Average value of urinary GH amount after Siberian larch extract) / (mean value of urinary GH amount after taking placebo) x 100

The average value of the change rate of urinary GH in the Siberian larch leaf extract was 123.1%.

The results of Example 6 and Comparative Example 5 show that by administering the Siberian larch leaf extract to a living body, the GH secretion of the living body is effectively promoted.

Hereinafter, a formulation of various compositions (final products) using the growth hormone secretagogue of the present invention is shown. In the following formulation, "Siberian larch (product name)" of Flavivir was used as Siberian larch leaf extract.

(Prescription Example 11: Tablets (7))

Siberian larch leaf extract 10 mg, lactose 60 mg, crystalline cellulose 170 mg, carboxymethyl cellulose-Ca 5 mg and sucrose fatty acid ester 5 mg were tableted by a conventional method.

(Prescription Example 12: Tablets (8))

The following materials were used to prepare tablets by the routine method.

108 mg of Siberian larch extract, 110 mg of sorbitol, 15 mg of partially pregelatinized starch, 75 mg of magnesium phosphate, 3 mg of calcium stearate, 40 mg of menthol particles and 5 mg of aspartame.

The assembly was prepared by adding 1900 g of erythritol and 300 g of cornstarch to 4000 g of a 6% by mass aqueous solution of hydroxypropyl cellulose. The average particle diameter was 290 탆.

(Prescription Example 13: Soft Capsules (5))

The following ingredients were used to prepare the contents of the soft capsule:

Siberian larch leaf extract 20 mg, vegetable oil 110 mg, glycerin fatty acid ester 10 mg, beeswax 10 mg.

Soft capsules were prepared by the usual method using the above ingredients and porcine gelatin.

[Industrial Availability]

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a growth hormone secretagogue which can be administered orally and is excellent in growth hormone secretion promoting effect.

Claims (7)

Characterized in that it comprises an olive extract as an active ingredient and an olive extract is an extract obtained from water or an alcohol or a mixed solvent of water and alcohol from all or a part of olive plants and the olive extract contains polyphenol Secretion promoter. The method according to claim 1,
A growth hormone secretagogue characterized in that all or part of the plant of olive comprises at least leaves, flowers or fruit of olive. The method according to claim 1,
The oral administration amount of olive extract is 0.1 to 1000 mg per day. The method according to claim 1,
Wherein the polyphenol comprises at least one selected from the group consisting of hydroxysterols, thyrosols, and oleoylphenes. Characterized in that it comprises an olive extract as an active ingredient and an olive extract is an extract derived from water, alcohol or a mixed solvent of water and alcohol from all or a part of olive plants and the olive extract contains polyphenol Food composition for promoting secretion. An olive extract is an extract obtained by extracting all or a portion of olive plants with water, an alcohol or a mixed solvent of water and alcohol, wherein the olive extract contains polyphenol, growth hormone secretion deficiency, growth Growth inhibition, cardiovascular disorder, and the like. An olive extract is an extract obtained by extracting all or a portion of olive plants with water, an alcohol or a mixed solvent of water and alcohol, wherein the olive extract contains polyphenol, growth hormone secretion deficiency, growth Growth disorder, cardiovascular disorder, and the like.